This invention is related to a method of inhibiting the activity of reverse transcriptase in viruses such as Rous sarcoma in warm-blooded animals such as chickens.
Reverse transcriptase (RNA dependent DNA polymerase) occurs uniquely in the virions of all members of a group of viruses which cause cancer in animals and probably in man. The viruses in this group include all of the transforming (sarcoma) C type viruses, the nontransforming (leukemia) C type viruses, and the mammary tumor (B type) virus. Also included are visna, maedi, and progressive pneumonia viruses which cause slow degenerative diseases and the foamy (syncytium forming) viruses. Visna and progressive pneumonia viruses can cause transformation of mouse cells in vitro. Human breast cancers contain an RNA related to that of mouse mammary tumor virus. The RNA is encapsulated with reverse transcriptase in a particle possessing the density characteristics of RNA tumor viruses (Axel, R., S. C. Gulati, and S. Spiegelman, Proc. Nat. Acad. Sci. U.S.G. 69, 3133 (1972). Similarly, complexes of RNA and reverse transcriptase have been identified in the white blood cells of leukemic patients (Baxt. W., R. Hehlmann, S. Spiegelman, Nature, 240, 72 (1972). Moreover, nononcogenic RNA viruses have been found to lack reverse transcriptase. The following viruses belong to this category: Reo, Polio, Influenza, Vesticular stomatitis, New Castle disease (Nature, 227, 1029 (1970). Evidence implicating reverse transcriptase in cell transformation is provided by the following observations:
1. A variant of Rous sarcoma virus RSV.alpha. (0) which failed to transform chick fibroblasts, lacked the enzyme (Hanafusa, H., and Hanafusa, T. Virology 43, 313 (1971);
2. A temperature sensitive mutant of Rous sarcoma virus which was unable either to transform or replicate at 41.degree.C. but could do both functions at 35.degree.C. contained reverse transcriptase, functional at 35.degree.C. but not at 41.degree.C. (Linial, M., and W. S. Mason, Virology 53, 258 (1973); and
3. The reverse transcriptase and transforming activities of Rous sarcoma virus could be destroyed by a chemical. However, the chemically inactivated virus recovered its transforming activity when coinfected with a nontransforming leukosis virus which possessed active reverse transcriptase (P. P. Hung, Virology 53, 463 (1973).